Ischemic stroke is the leading cause of disability with $2.2 trillion in projected costs of care over the next five decades in the United States alone. However, current stroke management is limited by the inability to measure the underlying physiology. The primary goal in the management of acute ischemic stroke and related brain injury is to maximize cerebral blood flow (CBF) in the affected region and surrounding penumbra. Because of the paucity of tools available for monitoring CBF in such patients, however, interventions to augment CBF are typically prescribed empirically based on expectations of neurological deficits, or in response to clinical deterioration. In the first fundig cycle, our Bioengineering Research Partnership (BRP) demonstrated that diffuse optical methods provide unique benefits for monitoring cerebrovascular physiology. Specifically, the BRP proved feasibility of optical CBF for stroke monitoring and confirmed individual variability of CBF responses. This research could not have been carried out without a unique multi-disciplinary team; or BRP team is comprised of clinical and biomedical investigators, with expertise in cerebrovascular physiology and neurocritical care, and physical scientists and engineers with expertise in optics, electronics, mathematics and computation. The proposed renewal BRP has evolved to contain three core components, a Biomedical Optics Group led by PI (Yodh), and two Clinical Groups focused on adult populations at the Hospital of the University of PA (Detre), and pediatric populations at the Children's Hospital of Philadelphia (Licht). The clinical and technological groups cross-inform the development and application processes, uncovering new ideas for clinical applications and new demands for technology. Proposed research will construct new probe- heads which emphasize the front-end of the device, in contact with the patient head, that address important limitations that have prevented wide-scale clinical adoption, and proposed research will broaden the clinical studies to ascertain cerebrovascular autoregulation responses in other management paradigms and in new patient groups such as pediatric populations eligible for Extra-Corporeal Membrane Oxygenation therapy, which will, in turn, create more opportunities for clinical translation. Technology commercialization and dissemination will be facilitated by Michael Poisel, Director of the UPSTART program in the Center for Technology Transfer (CTT) at Penn.